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Coggins C.R.E.,Carson Watts Consulting | Merski J.A.,Altria Client Services Inc. | Oldham M.J.,Altria Client Services Inc.
Inhalation Toxicology | Year: 2011

Context: Three heterocyclic nitrogen compounds, 2,3-diethylpyrazine (DEP), 2,3,5,6-tetramethylpyrazine (TMP), and 2-acetyl pyridine (AP), are naturally present in tobacco and are also added to tobacco as flavor ingredients. Objective: A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing the three heterocyclic nitrogen compounds added individually at three different levels. The lowest target inclusion level of the ingredient was 10 ppm, and the highest was 10,000 ppm. Material and methods: Smoke from experimental and control cigarettes was evaluated in analytical smoke chemistry, in vitro cytotoxicity, and mutagenicity assays. Results: The cigarettes with added DEP produced some minor (approximately 10%) changes in smoke chemistry when compared with the cigarettes containing no DEP. Smoke chemistry was effectively unchanged by the addition of either AP or TMP. Cytotoxicity, assessed by the neutral red uptake assay using both gas-vapor and particulate phases of smoke, was unaffected by the addition of any of the test ingredients. Mutagenicity, assessed in five strains of Salmonella treated with mainstream cigarette smoke condensate, also was unaffected by any of the test ingredients. Conclusions: Despite the exaggerated ingredient levels relative to commercial-use levels, there was a lack of a toxicological response for the three heterocyclic nitrogen compounds in the test systems used. © 2011 Informa Healthcare USA, Inc.


Coggins C.R.E.,Carson Watts Consulting | McKinney Jr. W.J.,Altria Client Services Inc. | Oldham M.J.,Altria Client Services Inc.
Inhalation Toxicology | Year: 2013

Context: Historical work indicates that cigarette circumference may affect the toxicological profile of experimental cigarettes. Objective: Studies were conducted to examine the effect of different cigarette circumferences on (1) selected mainstream smoke constituents including concentrations of tobacco specific nitrosamines (TSNA) in smoke and (2) mutagenicity and cytotoxicity of cigarette smoke condensate. Materials and methods: Analytical chemistry, Salmonella mutagenicity and cytotoxicity assays were used to evaluate the composition and biological activity of mainstream smoke from experimental, non-filtered cigarettes manufactured with four different circumferences (17.0-27.1mm). Results: Most smoke constituents, including TSNA, decreased with decreasing cigarette circumference; however, amounts of hydrogen cyanide increased in a non-circumference dependent manner. Mutagenicity and cytotoxicity also decreased slightly with decreasing cigarette circumference. Conclusion: Cigarette circumference may have a minor role in the toxicological profile of experimental cigarettes, with a so-far-unidentified mechanism. © 2013 Informa Healthcare USA, Inc.


Theophilus E.H.,R.J. Reynolds Tobacco Co | Coggins C.R.E.,Carson Watts Consulting | Chen P.,R.J. Reynolds Tobacco Co | Schmidt E.,R.J. Reynolds Tobacco Co | Borgerding M.F.,R.J. Reynolds Tobacco Co
Regulatory Toxicology and Pharmacology | Year: 2015

Tobacco toxicant-related exposure reduction is an important tool in harm reduction. Cigarette per day reduction (CPDR) occurs as smokers migrate from smoking cigarettes to using alternative tobacco/nicotine products, or quit smoking. Few reports characterize the dose-response relationships between CPDR and effects on exposure biomarkers, especially at the low end of CPD exposure (e.g., 5 CPD). We present data on CPDR by characterizing magnitudes of biomarker reductions. We present data from a well-controlled, one-week clinical confinement study in healthy smokers who were switched from smoking 19-25 CPD to smoking 20, 10, 5 or 0 CPD. Biomarkers were measured in blood, plasma, urine, and breath, and included smoke-related toxicants, urine mutagenicity, smoked cigarette filter analyses (mouth level exposure), and vital signs. Many of the biomarkers (e.g., plasma nicotine) showed strong CPDR dose-response reductions, while others (e.g., plasma thiocyanate) showed weaker dose-response reductions. Factors that lead to lower biomarker reductions include non-CPD related contributors to the measured response (e.g., other exposure sources from environment, life style, occupation; inter-individual variability). This study confirms CPDR dose-responsive biomarkers and suggests that a one-week design is appropriate for characterizing exposure reductions when smokers switch from cigarettes to new tobacco products. © 2015 The Authors.


Gaworski C.L.,Altria Client Services Inc. | Oldham M.J.,Altria Client Services Inc. | Wagner K.A.,Altria Client Services Inc. | Coggins C.R.E.,Carson Watts Consulting | Patskan G.J.,Altria Client Services Inc.
Inhalation Toxicology | Year: 2011

Context: Ingredients have been used in modern cigarette manufacturing to facilitate tobacco processing, provide flavor, and preserve tobacco. Concern has been raised regarding the use of ingredients in cigarette manufacturing due to the possible generation of toxic chemicals resulting from their combustion when added to tobacco. Objective: Investigate the impact of individual ingredients on cigarette smoke toxicity. Materials and methods: A total of 95 ingredients were tested individually through addition at different concentrations to the tobacco of experimental cigarettes. Mainstream cigarette smoke chemistry analysis, bacterial mutagenicity testing, and cytotoxicity testing were conducted. Additionally, 31 of the ingredients were tested in 90-day nose-only rat inhalation studies using mainstream cigarette smoke. Studies were designed following conventional toxicity testing methods employed for food additives and other consumer products. Results: The studies reported here demonstrate that high levels of some ingredients can change the quantity of some smoke constituents, altering the smoke chemistry profile. From the panel of biological endpoints monitored, these added ingredients produced minimal changes in the overall toxicity profile of mainstream cigarette smoke. In some cases, the addition of high levels of an ingredient caused a small reduction in toxicity findings, probably due to displacement of burning tobacco. Conclusion: The battery of testing results presented here is a useful addition to the available scientific information for cigarette ingredients and extends the dataset which can be used for evaluating their appropriate use. © 2011 Informa Healthcare USA, Inc.


Coggins C.R.E.,Carson Watts Consulting | Frost-Pineda K.,Altria Client Services Inc. | Smith D.C.,Altria Client Services Inc. | Oldham M.J.,Altria Client Services Inc.
Inhalation Toxicology | Year: 2011

Context: Various aromatic and aliphatic alcohol compounds are found in tobacco and tobacco smoke. Objective: A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing eight aromatic and aliphatic alcohol compounds that were added individually to experimental cigarettes at three different levels. The lowest target inclusion level was 100 ppm and the highest level was 24,400 ppm. Materials and methods: Mainstream smoke from each of the cigarette types was evaluated using analytical chemistry and assays to measure in vitro cytotoxicity (neutral red uptake) and Salmonella (five strains) mutagenicity. For three of the compounds (benzyl alcohol, propyl paraben, and rum flavor), 90-day smoke inhalation studies with 6-week recovery periods were also performed using rats. Results: Inclusion of eugenol produced several dose-related reductions in concentrations of selected smoke constituents. Cytotoxicity and mutagenicity were unaffected by any of the test ingredients, except for dose-related reductions in cytotoxicity of the gas vapor phase produced by the inclusion of eugenol. The three smoke inhalation studies showed a few sporadic differences between the groups and there were no differences in the patterns of recovery for any of the ingredients. Conclusions: Despite using exaggerated inclusion levels of the eight aliphatic and aromatic alcohol compounds in experimental cigarettes, there was minimal toxicological response, which is consistent with published reports of studies using mixtures of compounds added to tobacco. © 2011 Informa Healthcare USA, Inc.

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